This pilot study tests the susceptibility of simian aortic, pulmonary, and brain endothelium to infection by simian immunodeficiency virus (SIV) and the biologic response of cultured endothelium to viral exposure. Cultured lung and brain endothelial cultures are positive for Factor VIII and bind low density lipoprotein as expected for endothelium. We have demonstrated response of lung and brain endothelial cultures to stimulation with the cytokine TNF and have measured increased expression of activation antigens, HLA-DR, ICAM-1, VCAM-1, and ELAM-1. We have shown that activated endothelium can be infected with SIV and produce increasing amounts of virus over a two week period using antigen capture assay. Recent reports suggest that neurotropic viral variants more readily infect simian endothelium. That confirms and extends our findings and suggests future studies should exploit these viral strain differences.